Journal article
PKA Cβ: a forgotten catalytic subunit of cAMP-dependent protein kinase opens new windows for PKA signaling and disease pathologies
Publication Details
Authors: | Taylor, S.; Wallbott, M.; Machal, E.; Søberg, K.; Ahmed, F.; Bruystens, J.; Vu, L.; Baker, B.; Wu, J.; Raimondi, F.; Ongeri, E.; Herberg, F.; Skålhegg, B. |
Publication year: | 2021 |
Journal: | Biochemical Journal |
Pages range : | 2101-2119 |
Volume number: | 478 |
Issue number: | 11 |
ISSN: | 0264-6021 |
DOI-Link der Erstveröffentlichung: |
Abstract
3',5'-cyclic adenosine monophosphate (cAMP) dependent protein kinase or protein kinase A (PKA) has served as a prototype for the large family of protein kinases that are crucially important for signal transduction in eukaryotic cells. The PKA catalytic subunits are encoded by the two major genes PRKACA and PRKACB, respectively. The PRKACA gene encodes two known splice variants, the ubiquitously expressed C\textgreeka1 and the sperm-specifically expressed C\textgreeka2. In contrast, the PRKACB gene encodes several splice variants expressed in a highly cell and tissue-specific manner. The C\textgreekb proteins are called C\textgreekb1, C\textgreekb2, C\textgreekb3, C\textgreekb4 and so-called abc variants of C\textgreekb3 and C\textgreekb4. Whereas C\textgreekb1 is ubiquitously expressed, C\textgreekb2 is enriched in immune cells and the C\textgreekb3, C\textgreekb4 and their abc variants are solely expressed in neuronal cells. All C\textgreeka and C\textgreekb splice variants share a kinase-conserved catalytic core and a C-terminal tail encoded by exons 2 through 10 in the PRKACA and PRKACB genes, respectively. All C\textgreeka and C\textgreekb splice variants with the exception of C\textgreeka1 and C\textgreekb1 are hyper-variable at the N-terminus. Here, we will discuss how the PRKACA and PRKACB genes have developed as paralogs that encode distinct and functionally non-redundant proteins. The fact that C\textgreeka and C\textgreekb splice variant mutations are associated with numerous diseases further opens new windows for PKA-induced disease pathologies.
3',5'-cyclic adenosine monophosphate (cAMP) dependent protein kinase or protein kinase A (PKA) has served as a prototype for the large family of protein kinases that are crucially important for signal transduction in eukaryotic cells. The PKA catalytic subunits are encoded by the two major genes PRKACA and PRKACB, respectively. The PRKACA gene encodes two known splice variants, the ubiquitously expressed C\textgreeka1 and the sperm-specifically expressed C\textgreeka2. In contrast, the PRKACB gene encodes several splice variants expressed in a highly cell and tissue-specific manner. The C\textgreekb proteins are called C\textgreekb1, C\textgreekb2, C\textgreekb3, C\textgreekb4 and so-called abc variants of C\textgreekb3 and C\textgreekb4. Whereas C\textgreekb1 is ubiquitously expressed, C\textgreekb2 is enriched in immune cells and the C\textgreekb3, C\textgreekb4 and their abc variants are solely expressed in neuronal cells. All C\textgreeka and C\textgreekb splice variants share a kinase-conserved catalytic core and a C-terminal tail encoded by exons 2 through 10 in the PRKACA and PRKACB genes, respectively. All C\textgreeka and C\textgreekb splice variants with the exception of C\textgreeka1 and C\textgreekb1 are hyper-variable at the N-terminus. Here, we will discuss how the PRKACA and PRKACB genes have developed as paralogs that encode distinct and functionally non-redundant proteins. The fact that C\textgreeka and C\textgreekb splice variant mutations are associated with numerous diseases further opens new windows for PKA-induced disease pathologies.
